The compounds contemplated to be provided by the instant invention are 2,3-disubstituted levulinaldehydes of the general formula: ##SPC2##
Wherein n represents an integer from 5 to 8 inclusive and m represents zero or an integer from 1 to 5 inclusive.
As will be apparent to those skilled in the art, the structure shown in formula I has two centres of chirality, these two centres of chirality being at the carbon atoms in positions 2 and 3 respectively. Accordingly, all isomers of formula I, and mixtures thereof, are within the scope of the present invention.
Compounds of formula I are intermediates in the synthesis of highly biologically active cyclopentane derivatives known to those skilled in the art as "prostaglandins". Prostaglandins possess potent activities in the inhibition of gastric acid secretion, the production of hypotension, bronchodilation, the stimulation of uterine contraction, the production of hypocholesteraemia and hypolipidaemia and the stimulation of luteolysis.
The present invention seeks to provide intermediates useful in the preparation of prostaglandins of the PG.sub.1 series, that is prostaglandins containing a double bond in the 13, 14 position of prostanoic acid, for example, PGE.sub.1, PGA.sub.1, PGB.sub.1 PGF.sub.1.sub..alpha., or PGF.sub.1.sub..beta.. ##SPC3##
2,3-Disubstituted levulinaldehydes (D. P. Strike & H. Smith, U.S. Pat. No. 3,718,667) have previously been used in the synthesis of prostaglandins, but these compounds, because of their method of preparation, were restricted to the basic prostanoic acid structure, that is containing no 13,14-carbon-carbon double bond.
Although a number of methods are now available to the hereinbefore mentioned prostaglandins, (for example Merck & Co. Inc., U.S. Patent Application Ser. No. 201,979 of Nov. 24, 1971) a clear need exists for improved means, by fewer reaction steps and more readily accessible starting materials, to provide these therapeutically active compounds. The present invention provides such a means, requiring a smaller number of reaction steps, using inexpensive commercially available materials, to make 2,3-disubstituted levulinaldehydes, precursors for the hereinbefore mentioned prostaglandins.
It is the primary object of this invention, therefore, to provide 2,3-disubstituted levulinaldehydes by total synthesis from readily accessible starting materials, for use as intermediates in the synthesis of prostaglandins.